RESUMO
The ß-adrenergic blockers and antagonists of the renin-angiotensin system (RAS) are among the drugs that present better results in the control of cardio-metabolic diseases. The aim of the present study was to evaluate the effect of the association of the ß-blocker, atenolol, and an oral formulation of Ang-(1-7) on lipid metabolism in spontaneously hypertensive rats (SHR). The main results showed that SHR treated with oral formulation of Ang-(1-7) in combination to atenolol have an improvement of lipid metabolism with a reduction of total plasma cholesterol, improvement of oral fat load tolerance and an increase in the lipolytic response stimulated by the ß-adrenergic agonist, isoproterenol, without modification of resting glucose or insulin sensitivity in adipocytes. In conclusion, we showed that administration of an Ang-(1-7) oral formulation in association with a ß-blocker induces beneficial effects on dyslipidemia treatment associated with hypertension.
Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Angiotensina I/administração & dosagem , Angiotensina I/farmacologia , Atenolol/administração & dosagem , Atenolol/farmacologia , Hipertensão/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fragmentos de Peptídeos/administração & dosagem , Fragmentos de Peptídeos/farmacologia , Administração Oral , Antagonistas Adrenérgicos beta/administração & dosagem , Animais , Masculino , Ratos , Ratos Endogâmicos SHRRESUMO
This work describes chemical properties and anti-hypertensive activity of an oral pharmaceutical formulation obtained from the complexation of beta-cyclodextrin (beta-CD) with bradykinin potentiating penta peptide (BPP-5a) founded in the Bothrops jararaca poison. Physical chemistry characterizations were recorded in order to investigate the intermolecular interactions between species in complex. Circular dichroism data indicated conformational changes of BPP-5a upon complexation with beta-CD. ROESY and theoretical calculations showed a selective approximation of triptophan moiety into cavity of beta-CD. Isothermal titration calorimetry data indicated an exothermic formation of the complex, which is accomplished by reduction of entropy. The anti-hypertensive activity of the BPP-5a/beta-CD complex has been evaluated in spontaneous hypertensive rats, showing better results than pure BPP-5a.